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Microbial communities have evolved to colonize all ecosystems of the planet, from the deep sea to the human gut. Microbes survive by sensing, responding, and adapting to immediate environmental cues. This process is driven by signal transduction proteins such as histidine kinases, which use their sensing domains to bind or otherwise detect environmental cues and "transduce" signals to adjust internal processes. We hypothesized that an ecosystem's unique stimuli leave a sensor "fingerprint," able to identify and shed insight on ecosystem conditions. To test this, we collected 20,712 publicly available metagenomes from Host-associated, Environmental, and Engineered ecosystems across the globe. We extracted and clustered the collection's nearly 18M unique sensory domains into 113,712 similar groupings with MMseqs2. We built gradient-boosted decision tree machine learning models and found we could classify the ecosystem type (accuracy: 87%) and predict the levels of different physical parameters (R2 score: 83%) using the sensor cluster abundance as features. Feature importance enables identification of the most predictive sensors to differentiate between ecosystems which can lead to mechanistic interpretations if the sensor domains are well annotated. To demonstrate this, a machine learning model was trained to predict patient's disease state and used to identify domains related to oxygen sensing present in a healthy gut but missing in patients with abnormal conditions. Moreover, since 98.7% of identified sensor domains are uncharacterized, importance ranking can be used to prioritize sensors to determine what ecosystem function they may be sensing. Furthermore, these new predictive sensors can function as targets for novel sensor engineering with applications in biotechnology, ecosystem maintenance, and medicine.IMPORTANCEMicrobes infect, colonize, and proliferate due to their ability to sense and respond quickly to their surroundings. In this research, we extract the sensory proteins from a diverse range of environmental, engineered, and host-associated metagenomes. We trained machine learning classifiers using sensors as features such that it is possible to predict the ecosystem for a metagenome from its sensor profile. We use the optimized model's feature importance to identify the most impactful and predictive sensors in different environments. We next use the sensor profile from human gut metagenomes to classify their disease states and explore which sensors can explain differences between diseases. The sensors most predictive of environmental labels here, most of which correspond to uncharacterized proteins, are a useful starting point for the discovery of important environment signals and the development of possible diagnostic interventions.

Here, we describe "obelisks," a class of heritable RNA elements sharing several properties: (1) apparently circular RNA ∼1 kb genome assemblies, (2) predicted rod-like genome-wide secondary structures, and (3) open reading frames encoding a novel "Oblin" protein superfamily. A subset of obelisks includes a variant hammerhead self-cleaving ribozyme. Obelisks form their own phylogenetic group without detectable similarity to known biological agents. Surveying globally, we identified 29,959 distinct obelisks (clustered at 90% sequence identity) from diverse ecological niches. Obelisks are prevalent in human microbiomes, with detection in ∼7% (29/440) and ∼50% (17/32) of queried stool and oral metatranscriptomes, respectively. We establish Streptococcus sanguinis as a cellular host of a specific obelisk and find that this obelisk's maintenance is not essential for bacterial growth. Our observations identify obelisks as a class of diverse RNAs of yet-to-be-determined impact that have colonized and gone unnoticed in human and global microbiomes. [Display omitted] • Obelisks are a phylogenetically distinct group of microbiome-associated, viroid-like RNAs • Found globally in diverse niches, obelisks also occur in human stool and oral microbiomes • The human oral bacterium Streptococcus sanguinis SK36 harbors a distinct "obelisk- S.s " • Under replete growth conditions, obelisk- S.s appears to be disposable for SK36 growth Obelisks are widespread RNA-based agents found in diverse environmental and human-associated microbiomes. These apparently unbranched and circular RNAs represent a previously uncharacterized class of genetic elements. [ABSTRACT FROM AUTHOR]

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium. [ABSTRACT FROM AUTHOR]

Introduction: Although the oral cavity and the gut are anatomically continuous regions of the gastrointestinal tract, research on the relationship between oral and gut microbiota remains sparse. Oral-gut bacterial translocation is mostly studied in pathological contexts, thus evidence of translocation in healthy conditions is still scarce. Studying the oral-gut microbiota relationship in humans in different life stages is necessary in order to understand how these microbial communities might relate throughout life. Methods: In this study, saliva and fecal samples were collected from healthy participants (39 children, 97 adults). Microbiota analysis was carried out by sequencing the V4 region of the 16S ribosomal RNA gene, followed by amplicon sequence variant (ASV) analysis. Results and discussion: Although the oral and gut microbiota are vastly different, a subset of 61 ASVs were present in both the oral cavity and gut of the same individual, and represented 1.6% of all ASVs detected. From these, 26 ASVs (classified into 18 genera: Actinomyces , Rothia , Bacteroides , Porphyromonas , Prevotella , Alistipes , Fusobacterium , Neisseria , Haemophilus , Akkermansia , Solobacterium , Granulicatella , Streptococcus , Gemella , Mogibacterium , Dialister , Veillonella , Christensenellaceae R-7 group) were present in both children and adults, suggesting the possibility of persistent colonization of both habitats by these microorganisms, initiating in childhood. Additionally, 62% of shared ASVs were more abundant in the oral cavity, indicating that oral-to-gut translocation may be the main route of translocation between environments, and highlighting that this phenomenon might be more common than previously thought in healthy individuals of all ages. [ABSTRACT FROM AUTHOR]

Introduction: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites. Methods: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities. Results: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples. Discussion: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. [ABSTRACT FROM AUTHOR]

Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD. [ABSTRACT FROM AUTHOR]

Background: Green tea kombucha (GTK) is a fermented beverage with promising health benefits, but few studies proved its impact on human health. Thus, we aimed to investigate the impact of GTK on weight loss, inflammation, and salivary microbiota in individuals with excess body weight. Methods: This is a randomized controlled clinical trial that lasted 10 weeks with two groups of individuals with excess body weight: control (CG; n = 29; caloric restriction) and kombucha (KG; n = 30; caloric restriction + 200 mL GTK). Body composition, anthropometry, saliva, and blood collection were performed in the beginning and end of the intervention. Plasma interleukins were determined by flow cytometry. Salivary microbiota was analyzed by 16S rRNA sequencing. Results: Both groups decreased weight, BMI, and body fat (p < 0.001) after the intervention, but there were no differences between groups. The KG reduced lipid accumulation product (LAP) (p = 0.029). Both groups decreased IL-1β and IL-8, but IL-6 increased in the CG (p = 0.023) compared to the kombucha group. Alpha and beta diversity of salivary microbiota increased in the KG. Moreover, the KG presented lower Bacillota/Bacteroidota ratio (p = 0.028), and BMI was positively associated with the Bacillota phylum. Conclusions: GTK did not enhance weight loss, but it decreased the LAP. GTK helped in the inflammatory profile and induced positive changes in oral microbiota composition. [ABSTRACT FROM AUTHOR]

Organisms display an immense variety of shapes, sizes, and reproductive strategies. At microscopic scales, bacterial cell morphology and growth dynamics are adaptive traits that influence the spatial organization of microbial communities. In one such community--the human dental plaque biofilm--a network of filamentous Corynebacterium matruchotii cells forms the core of bacterial consortia known as hedgehogs, but the processes that generate these structures are unclear. Here, using live-cell time-lapse microscopy and fluorescent D-amino acids to track peptidoglycan biosynthesis, we report an extraordinary example of simultaneous multiple division within the domain Bacteria. We show that C. matruchotii cells elongate at one pole through tip extension, similar to the growth strategy of soil-dwelling Streptomyces bacteria. Filaments elongate rapidly, at rates more than five times greater than other closely related bacterial species. Following elongation, many septa form simultaneously, and each cell divides into 3 to 14 daughter cells, depending on the length of the mother filament. The daughter cells then nucleate outgrowth of new thinner vegetative filaments, generating the classic "whip handle" morphology of this taxon. Our results expand the known diversity of bacterial cell cycles and help explain how this filamentous bacterium can compete for space, access nutrients, and form important interspecies interactions within dental plaque. [ABSTRACT FROM AUTHOR]

In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server (http://mimedsurv.micloud.kr). [ABSTRACT FROM AUTHOR]

Forensic microbiology is rapidly emerging as a novel tool for human identification. The human microbiome, comprising diverse microbial communities including fungi, bacteria, protozoa, and viruses, is unique to each individual, offering a new dimension to forensic investigations. While traditional identification methods primarily rely on DNA profiling and fingerprint analysis, they face limitations when complete DNA or fingerprints profiles are unattainable or degraded. In this context, the microbial signatures of the human skin microbiome present a promising alternative due to their resilience to environmental stresses and individual-specific composition. This review explores the potential of microbiome analysis in forensic human identification, evaluating its applications, advantages, limitations, and future prospects. The uniqueness of an individual's microbial community, particularly the skin microbiota, can provide distinctive biological markers for identification purposes, while technological advancements like 16 S rRNA sequencing and metagenomic shotgun sequencing are enhancing the specificity of microbial identification, enabling detailed analysis of these complex ecological communities. Despite these promising findings, current research has not yet achieved a level of identification probability that could establish microbial analysis as a stand-alone evidence tool. Therefore, it is presently considered ancillary to traditional methods, contributing to a more comprehensive biological profile of individuals. [ABSTRACT FROM AUTHOR]

Abstract The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.

In recent years, a vast array of thinkers have been invested in challenging the long-standing binary division between the human and nonhuman. The notion of the human microbiome especially attests to the truth of such a complication, since current research in biology strongly suggests that we are at the very least as much microbe as we are human and that the number of microorganisms in the human body outnumber distinctly human cells considerably. In this article, we aim to bring the biological notion of the human microbiome in dialogue with Object-Oriented Ontology (OOO) so as to ultimately show that there can be a fruitful exchange of ideas between the two currents of microbiome research and OOO more specifically, and that Graham Harman’s top-down account of objective emergence can be fruitfully a bottom-up approach according to which the parts of an object also impact and constrain the whole.

Abstract In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server ( http://mimedsurv.micloud.kr ).

Objective: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines. Materials and methods: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts. Results: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle–Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls. Conclusions: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Archaea represent a separate domain of life, next to bacteria and eukarya. As components of the human microbiome, archaea have been associated with various diseases, including periodontitis, endodontic infections, small intestinal bacterial overgrowth, and urogenital tract infections. Archaea are generally considered nonpathogenic; the reasons are speculative because of limited knowledge and gene annotation challenges. Nevertheless, archaeal syntrophic principles that shape global microbial networks aid both archaea and potentially pathogenic bacteria. Evaluating archaea interactions remains challenging, requiring clinical studies on inflammatory potential and the effects of archaeal metabolism. Establishing a culture collection is crucial for investigating archaea functions within the human microbiome, which could improve health outcomes in infectious diseases. We summarize potential reasons for archaeal nonpathogenicity, assess the association with infectious diseases in humans, and discuss the necessary experimental steps to enable mechanistic studies involving archaea.

Establishing geographical location is a crucial aspect of forensic sciences, distinguishing between primary and secondary crime scenes, linking an individual to a crime scene, or detecting sources of disease. Microorganisms can be used as geolocation indicators since microbial communities vary according to climatic factors (e.g. temperature, humidity, soil properties, altitude). Therefore, this systematic review aimed to investigate whether the human or environmental microbiomes help to determine a crime's geolocation. Articles were searched in PubMed,Scopus and Web of Science using keywords and data fields. The final selection included seven (of 172) manuscripts. The results showed that the microbial profile of either human or environmental samples have the potential to link a cadaver or a crime scene to a given location, highlighting microbes' usefulness in obtaining information from geographical locations (e.g. soil samples from a suspect's shoe matched to a source). However, research is required before applying this forensic strategy to real scenarios. For instance, optimizing and standardizing the microbiome analysis methods and determining several factors that may influence the results. [ABSTRACT FROM AUTHOR]

The use of medicinal plants has increased tremendously and that has led to the scientific interest for testing this plant for toxicity and antimicrobial activity. The manuscript used a comprehensive literature search from databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant studies published within the last five years (2018-2023) and selectively those beyond that provide the necessary background to the article. The literature analysis found a huge scientific progress made and a lot of plants have been tested for safe use and antimicrobial resistance using the different microorganisms. Nonetheless, the article also highlights the possible hormonal effect or microbiota imbalance which could be attributed to these medical plants being used without proper guidance among our population. Age wise on patients, any prolonged use of these medicinal plants may have devastating effects as such this article advocates for a thorough understanding of the normal flora when communities are treated at home by traditional healers. [ABSTRACT FROM AUTHOR]

This paper tried to analyze publications on "Human microbiome," globally over the last 22 years i.e. 2002- 2023 and summarize the most advanced achievements in this field, data retrieved from SCOPUS database. The total 3814 number of research publications found and extracted and further analyzed in selected parameters for fulfillment of the objectives of the study. This research aims to assess the global research productivity on the "Human microbiome." In respect of Literature Publications "United States" is at the top among the world with publications (TP=1858), followed by "China (TP=321)", "United Kingdom (TP=234)", "Germany (TP=216)", "Canada (TP=213)" and "India (TP=183)" in this field during this time. "Frontiers in Microbiology" is the most presiding journal in the field of "Human Microbiome" with 113 publications followed by "Plos One" with 100 publications. We use an open-source tool, VOSviewer for classic logical bibliometric analysis. [ABSTRACT FROM AUTHOR]

Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding betweenmicrobiologists andmodelers/bioinformaticians, stemming froma lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored formicrobiologists, researchers newtomicrobiomemodeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling. [ABSTRACT FROM AUTHOR]

This article reformulates Stephan Helmreich´s the ¨microbiomisation of race¨ as the historiality of otherness in the foundations of human microbiome science. Through the lens of my ethnographic fieldwork of a transnational community of microbiome scientists that conducted a landmark human microbiome research on indigenous microbes and its affiliated and first personalised microbiome initiative, the American Gut Project, I follow and trace the key actors, experimental systems and onto-epistemic claims in the emergence of human microbiome science a decade ago. In doing so, I show the links between the reinscription of race, comparative research on the microbial genetic variation of human populations and the remining of bioprospected data for personalised medicine. In these unpredictable research movements, the microbiome of non-Western peoples and territories is much more than a side project or a specific approach within the field: it constitutes the nucleus of its experimental system, opening towards subsequent and cumulative research processes and knowledge production in human microbiome science. The article demonstrates that while human microbiome science is articulated upon the microbial 'makeup' of non-wester(nised) communities, societies, and locales, its results and therapeutics are only applicable to medical conditions affecting rich nations (i.e., inflammatory, autoimmune, and metabolic diseases). My reformulation of ¨microbiomisation of race¨ as the condition of possibility of human microbiome science reveals that its individual dimension is sustained by microbial DNA data from human populations through bioprospecting practices and gains meaning through personalised medicine initiatives, informal online networks of pseudoscientific and commodified microbial-related evidence. [ABSTRACT FROM AUTHOR]

Different modifications of the standard bread recipe have been proposed to improve its nutritional and health benefits. Here, we utilized the in vitro Human Gut Simulator (HGS) to assess the fermentation of one such artisan bread by human gut microbiota. Dried and milled bread, composed of almond flour, psyllium husks, and flax seeds as its three main ingredients, was first subjected to an in vitro protocol designed to mimic human oro-gastro-intestinal digestion. The bread digest was then supplied to complex human gut microbial communities, replacing the typical Western diet-based medium (WM) of the GHS system. Switching the medium from WM to bread digest resulted in statistically significant alterations in the community structure, encoded functions, produced short-chain fatty acids, and available antioxidants. The abundances of dietary fiber degraders Enterocloster, Mitsuokella, and Prevotella increased; levels of Gemmiger, Faecalibacterium, and Blautia decreased. These community alterations resembled the previously revealed differences in the distal gut microbiota of healthy human subjects consuming typical Mediterranean vs. Western-pattern diets. Therefore, the consumption of bread high in dietary fiber and unsaturated fatty acids might recapitulate the beneficial effects of the Mediterranean diet on the gut microbiota. [ABSTRACT FROM AUTHOR]

ABSTRACT The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.

ABSTRACT The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 102 copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.

ABSTRACT The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

ABSTRACT Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host–microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitzii and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.IMPORTANCEOutcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes.

ABSTRACT Medical modulation of sex hormone levels is a cornerstone of treatment for many conditions that impact well-being, including cancer, fertility/infertility, gender dysphoria, and chronic metabolic diseases such as diabetes and obesity. The microbial residents of the intestine, known as the microbiota, interact with sex hormones in the intestine, and there is correlative evidence that this interaction is bidirectional. Based on these published findings, we hypothesized that transgender individuals receiving exogenous testosterone as part of their gender-affirming medical treatment might undergo changes in their intestinal microbiome. To test this, we collected 26 stool samples from nine individuals before and up to 8 months after initiation of treatment with exogenous testosterone and subjected these samples to metagenomic analysis. While no species were significantly associated with the duration of testosterone therapy, pathways that generate glutamate increased in abundance, while those that consume glutamate decreased. Glutamate is a precursor of arginine, and testosterone is known to increase levels of arginine and its metabolites in the plasma. We hypothesize that testosterone increases the uptake of glutamate by enterocytes, thus decreasing access of the microbiota to this amino acid. While this pilot study establishes the impact of testosterone therapy on the intestinal microbiome, a more comprehensive study is necessary to establish the impact of testosterone-driven metagenomic shifts on the stool metatranscriptome, the stool metabolome, and the plasma metabolome.IMPORTANCEThe human intestine is inhabited by a large community of microbes known as the microbiome. Members of the microbiome consume the diet along with their human host. Thus, the metabolomes of the host and microbe are intricately linked. Testosterone alters the plasma metabolome. In particular, plasma levels of arginine and its metabolites and testosterone are positively correlated. To investigate the impact of exogenous testosterone on the microbiome, we analyzed the stool metagenomes of transgender individuals before and after the initiation of testosterone treatment. In this pilot project, we found a modest impact on the microbiome community structure but an increase in the abundance of metabolic pathways that generate glutamate and spare glutamate consumption. We propose that the host uses glutamate to generate arginine, decreasing the amount available for the microbiome.

IntroductionAlthough the oral cavity and the gut are anatomically continuous regions of the gastrointestinal tract, research on the relationship between oral and gut microbiota remains sparse. Oral-gut bacterial translocation is mostly studied in pathological contexts, thus evidence of translocation in healthy conditions is still scarce. Studying the oral-gut microbiota relationship in humans in different life stages is necessary in order to understand how these microbial communities might relate throughout life.MethodsIn this study, saliva and fecal samples were collected from healthy participants (39 children, 97 adults). Microbiota analysis was carried out by sequencing the V4 region of the 16S ribosomal RNA gene, followed by amplicon sequence variant (ASV) analysis.Results and discussionAlthough the oral and gut microbiota are vastly different, a subset of 61 ASVs were present in both the oral cavity and gut of the same individual, and represented 1.6% of all ASVs detected. From these, 26 ASVs (classified into 18 genera: Actinomyces, Rothia, Bacteroides, Porphyromonas, Prevotella, Alistipes, Fusobacterium, Neisseria, Haemophilus, Akkermansia, Solobacterium, Granulicatella, Streptococcus, Gemella, Mogibacterium, Dialister, Veillonella, Christensenellaceae R-7 group) were present in both children and adults, suggesting the possibility of persistent colonization of both habitats by these microorganisms, initiating in childhood. Additionally, 62% of shared ASVs were more abundant in the oral cavity, indicating that oral-to-gut translocation may be the main route of translocation between environments, and highlighting that this phenomenon might be more common than previously thought in healthy individuals of all ages.

IntroductionAccurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites.MethodsCHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities.ResultsCHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples.DiscussionTaken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.

ABSTRACT The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity. Using the protein domain (Pfam) frequencies from 61 bacterial species with experimentally determined D10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive (D10 < 200 Gy) and radiation-tolerant (D10 > 200 Gy) bacteria. On untrained species, TolRad had an accuracy of 0.900. We applied TolRad to 152 UniProt-hosted bacterial proteomes associated with the human microbiome, including 37 strains from the ATCC Human Microbiome Collection, and classified 34 species as radiosensitive. Whereas IR-sensitive species (D10 < 200 Gy) in the training data set had been confined to the phylum Proteobacterium, this initial TolRad screen identified radiosensitive bacteria in two additional phyla. We experimentally validated the predicted radiosensitivity of a Bacteroidota species from the human microbiome. To demonstrate that TolRad can be applied to metagenome-assembled genomes (MAGs), we tested the accuracy of TolRad on Egg-NOG assembled proteomes (0.965) and partial proteomes. Finally, three collections of MAGs were screened using TolRad, identifying further phyla with radiosensitive species and suggesting that environmental conditions influence the abundance of radiosensitive bacteria.IMPORTANCEBacterial species have vast genetic diversity, allowing for life in extreme environments and the conduction of complex chemistry. The ability to harness the full potential of bacterial diversity is hampered by the lack of high-throughput experimental or bioinformatic methods for characterizing bacterial traits. Here, we present a computational model that uses de novo-generated genome annotations to classify a bacterium as tolerant of ionizing radiation (IR) or as radiosensitive. This model allows for rapid screening of bacterial communities for low-tolerance species that are of interest for both mechanistic studies into bacterial sensitivity to IR and biomarkers of IR exposure.

When examining bacterial genomes for evidence of past selection, the results depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by dN/dS, the normalized ratio of nonsynonymous to synonymous mutations. Here, we show that the classical interpretation of this scale dependence, weak purifying selection, leads to problematic mutation accumulation when applied to available gut microbiome data. We propose an alternative, adaptive reversion model with opposite implications for dynamical intuition and applications of dN/dS. Reversions that occur and sweep within-host populations are nearly guaranteed in microbiomes due to large population sizes, short generation times, and variable environments. Using analytical and simulation approaches, we show that adaptive reversion can explain the dN/dS decay given only dozens of locally fluctuating selective pressures, which is realistic in the context of Bacteroides genomes. The success of the adaptive reversion model argues for interpreting low values of dN/dS obtained from long timescales with caution as they may emerge even when adaptive sweeps are frequent. Our work thus inverts the interpretation of an old observation in bacterial evolution, illustrates the potential of mutational reversions to shape genomic landscapes over time, and highlights the importance of studying bacterial genomic evolution on short timescales.

Abstract The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

The human body harbors an extremely complex and dynamic microbial community (10-100 trillion) of bacteria, archaea, viruses, and eukaryotes. The human microbiota plays a crucial role in the environment and human health under normal circumstances; nonetheless, dysfunction of the human microbiome has been associated with illnesses ranging from inflammatory bowel disease to multidrug-resistant infections. Culture-dependent human microbial exploration approaches are inadequate for discovering the diversity, abundance, and full genetic and metabolic potential of the whole microbial ecosystem. Hence, metagenomics analysis is a powerful advanced technology for comprehensively studying human microbial composition and diversity, exploring novel and antibiotic resistance genes, microbial metabolic pathways, functional dysbiosis, and co-evolution of the microbiome with the host. Therefore, owing to the increase in human microbiome sequencing projects in healthy and diseased people worldwide, it is feasible to explore the human microbiome using a metagenomics approach. Thus, this review focuses on the advancement of metagenomics for exploring the human microbiome, human microbiome metagenomics data processing, and analysis strategies. Currently used bioinformatics tools and their approaches are also discussed in the context of human microbial metagenomics.

The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health. [ABSTRACT FROM AUTHOR]

The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI- (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile's resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI. [ABSTRACT FROM AUTHOR]

It is becoming increasingly clear that the human microbiota, also known as “the hidden organ”, possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis. [ABSTRACT FROM AUTHOR]

Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing. [ABSTRACT FROM AUTHOR]

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Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.

ABSTRACT Bacterial isolates from the human urinary microbiome have been extensively studied for their antibiotic resistance; however, little work has been done on those isolates that are difficult to grow in vitro. This study was designed to qualify a serum-based medium, New York City Broth III (NYCIII), and a broth microdilution method to determine the antibiotic susceptibility of previously underreported or undescribed microbes that have a difficult time growing in standard Mueller-Hinton broth. Here, we demonstrate that NYCIII microbroth dilution can be an effective method for the determination of antibiotic susceptibility of species found in the human urinary microbiome. We show that this method serves well to characterize fastidious and anaerobic urinary microbes that have no Clinical and Laboratory Standards Institute (CLSI) guidelines, including several in the families Aerococcaceae, Lactobacillaceae, or Actinomycetaceae. Previous studies using expanded quantitative urine culture reveal that urine samples from clinical patients are commonly polymicrobial in composition. Thus, we test whether NYCIII can serve as a viable harmonized medium, capable of supporting antibiotic susceptibility testing in a range of fastidious, non-fastidious, and anaerobic urinary microbes. We propose this methodology to be standardized comparable to CLSI standards to allow for resistance testing in uncharacterized urinary bacteria.IMPORTANCEAntibiotic susceptibilities of fastidious and anaerobic bacteria of the human urinary microbiome are largely underreported due to difficulty in growing them in the lab environment. The current standard medium, Muller-Hinton broth, has difficulty supporting the growth of many of these species, leaving microbiologists without a standardized method. To address this need, this study offers a methodology to survey susceptibilities in a high-throughput manner of these understudied microbes with a proposed harmonized medium, NYCIII, which is capable of supporting the growth of both fastidious and non-fastidious urinary microbes. Broader standardization of this method can allow for the development of antibiotic-resistant breakpoints of the many uncharacterized urinary microbes.

Objective: comprehensive analysis of the spectrum of antibacterial action of bactеriocins.Material and methods. Chemomicrobiome analysis of bacteriocins A/B, C, S, 28b, RS-2020 was performed to assess the minimum inhibitory concentration (MIC) values for 152 strains of pathogenic bacteria and the area under the growth curve (AUC) values for a representative sample of normobiota (38 human commensal bacteria).Results. Compared to other molecules, bacteriocin C was characterized by lower MIC constants for a wide range of pathogenic bacterial strains. Thus, it more effectively inhibited strains of pathogens of bacterial pneumonia (H. influenzae, S. mutans, S. pneumoniae, S. pyogenes), nosocomial infections (K. pneumoniae, P. aeruginosa, S. aureus, S. epidermidis, S. pneumoniae), skin diseases (M. audouinii, T. mentagrophytes, etc.), urinary tract infections (E. cloacae, P. mirabilis and P. vulgaris), Fusobacterium necrophorum and Candida fungi. At the same time, bacteriocin C to a lesser extent than the reference molecules inhibited the growth of the normophysiological microbiota of the Bacteroides, Enterococcus genera, non-pathogenic Escherichia, yeast S. cerevisiae and others. By stimulating butyrate (butyric anion) producing microorganisms, bacteriocin C can exhibit prebiotic properties.Conclusion. The main structural features of the bacteriocin C molecule associated with the antibacterial effect on pathogenic microbiota were identified and described.

Abstract Objectives This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. Materials and Methods Fifty‐two adult volunteers aged 30–60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per‐protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). Results At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. Conclusions CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140.

Background: Green tea kombucha (GTK) is a fermented beverage with promising health benefits, but few studies proved its impact on human health. Thus, we aimed to investigate the impact of GTK on weight loss, inflammation, and salivary microbiota in individuals with excess body weight. Methods: This is a randomized controlled clinical trial that lasted 10 weeks with two groups of individuals with excess body weight: control (CG; n = 29; caloric restriction) and kombucha (KG; n = 30; caloric restriction + 200 mL GTK). Body composition, anthropometry, saliva, and blood collection were performed in the beginning and end of the intervention. Plasma interleukins were determined by flow cytometry. Salivary microbiota was analyzed by 16S rRNA sequencing. Results: Both groups decreased weight, BMI, and body fat (p < 0.001) after the intervention, but there were no differences between groups. The KG reduced lipid accumulation product (LAP) (p = 0.029). Both groups decreased IL-1β and IL-8, but IL-6 increased in the CG (p = 0.023) compared to the kombucha group. Alpha and beta diversity of salivary microbiota increased in the KG. Moreover, the KG presented lower Bacillota/Bacteroidota ratio (p = 0.028), and BMI was positively associated with the Bacillota phylum. Conclusions: GTK did not enhance weight loss, but it decreased the LAP. GTK helped in the inflammatory profile and induced positive changes in oral microbiota composition.

Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn’s disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.